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The New England Journal of Medicine Aug 2002Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited.
METHODS
We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks.
RESULTS
A total of 101 children (82 boys and 19 girls; mean [+/-SD] age, 8.8+/-2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg, as compared with 0.8+/-2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months.
CONCLUSIONS
Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.
Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Child; Child Behavior; Child, Preschool; Double-Blind Method; Female; Humans; Male; Risperidone; Treatment Outcome
PubMed: 12151468
DOI: 10.1056/NEJMoa013171 -
Profiles of Drug Substances,... 2012
Review
Topics: Animals; Antipsychotic Agents; Drug Stability; Humans; Risperidone; Spectrum Analysis
PubMed: 22469322
DOI: 10.1016/B978-0-12-397220-0.00008-8 -
Chemico-biological Interactions Jan 2023As the second-oldest atypical antipsychotic, risperidone has a long history of off-label usage for treating behavioural and psychological signs and symptoms of dementia... (Review)
Review
As the second-oldest atypical antipsychotic, risperidone has a long history of off-label usage for treating behavioural and psychological signs and symptoms of dementia (BPSD), such as agitation, aggressiveness, and psychosis. Risperidone has been shown in several trials to have a statistically significant benefit when used in a therapeutic context. Several lines of evidence suggest a possible role of risperidone via the antagonistic effect of Dopamine D2 and 5HT-receptor in different neurological diseases like cognitive dysfunction of schizophrenia, neuroinflammation, Huntington's disease, and sleep cycle management. Therefore, the pharmacological interactions of risperidone in all these diseases were investigated. Some reports on the use of risperidone in the treatment of dopaminergic psychosis have been slightly conflicting. However, more research is needed to evaluate the role of risperidone in the treatment of these neurological diseases.
Topics: Humans; Risperidone; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Huntington Disease
PubMed: 36496108
DOI: 10.1016/j.cbi.2022.110296 -
Advances in Therapy Nov 2022Antipsychotics are the cornerstone of schizophrenia treatment. Lack of treatment adherence encouraged the development of injectable long-acting antipsychotics. However,... (Review)
Review
Antipsychotics are the cornerstone of schizophrenia treatment. Lack of treatment adherence encouraged the development of injectable long-acting antipsychotics. However, second-generation or atypical antipsychotics require a loading dose at the start of treatment and eventually oral supplementation to achieve therapeutic plasma levels. This review discusses the evidence emerging from studies evaluating the pharmacokinetics, efficacy and safety of the intramuscular formulation of risperidone based on in situ microparticles (ISM). ISM® technology applied to risperidone allows therapeutic levels of the active moiety to be achieved within 2 h of intramuscular administration without the need for loading doses or oral supplementation, leading to a constant release over the whole dosing period. Risperidone ISM showed significant antipsychotic efficacy versus placebo in the Positive and Negative Syndrome Scale (PANSS) total score (p < 0.0001) and on the subscales of positive symptoms after 8 days, negative symptoms in 8 weeks, and general psychopathology during the 12 weeks of treatment. The improvement was also statistically significant (p < 0.0001) against placebo in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score at the end of the treatment. Risperidone ISM was generally well tolerated and the most frequently reported adverse events were similar to those observed with other risperidone formulations. There is clinical evidence that these results are maintained in the long term. In conclusion, four-weekly risperidone ISM (75 mg and 100 mg) is an adequate antipsychotic for treating schizophrenia, both in the short term when an exacerbation has recently occurred and for long-term maintenance, since it provides rapid onset of action and sustained efficacy, as well as being safe and well tolerated.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Humans; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Treatment Outcome
PubMed: 36048404
DOI: 10.1007/s12325-022-02299-8 -
The Annals of Pharmacotherapy Dec 2004To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of long-acting (LA) risperidone for the treatment of schizophrenia. (Review)
Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of long-acting (LA) risperidone for the treatment of schizophrenia.
DATA SOURCES
Information was selected from PubMed (1965-July 2004). Applicable scientific posters were also used.
STUDY SELECTION AND DATA EXTRACTION
All published information on risperidone LA was considered. Material providing a comprehensive description was considered.
DATA SYNTHESIS
Risperidone LA is the first long-acting, injectable atypical antipsychotic. It is dosed at 25-50 mg every 2 weeks. Adverse effects are similar to those seen with oral risperidone. A short-term study showed that risperidone LA is better than placebo in reducing the signs and symptoms of schizophrenia, and a long-term trial showed that stable schizophrenic patients can be switched from either oral or other injectable antipsychotic medications to risperidone LA.
CONCLUSIONS
Risperidone LA is efficacious and safe in the treatment of schizophrenia.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Drug Administration Schedule; Humans; Injections, Intramuscular; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia
PubMed: 15522979
DOI: 10.1345/aph.1E085 -
ACS Chemical Neuroscience Jul 2018After the identification of the influence of serotonergic receptors in ameliorating the negative symptoms associated with schizophrenia, atypical antipsychotics were... (Review)
Review
After the identification of the influence of serotonergic receptors in ameliorating the negative symptoms associated with schizophrenia, atypical antipsychotics were developed by incorporating dopamine and serotonin antagonism. Risperidone, sold under the trade name Risperdal, was the second atypical antipsychotic developed following clozapine but quickly became a first-line treatment for acute and chronic schizophrenia because of its preferential side effect profile. Despite initial Food and Drug Administration approval 25 years ago, risperidone continues to be a fundamental treatment for schizophrenia, bipolar I disorder, and autism-related irritability. It is on the World Health Organization's List of Essential Medicines for its balance of efficacy, safety, tolerability, and cost-effectiveness. In this review, we highlight the history and importance of risperidone as an atypical antipsychotic, in addition to its chemical synthesis, manufacturing, drug metabolism and pharmacokinetics, pharmacology, structure-activity relationship, indications, and adverse effects.
Topics: Animals; Humans; Mental Disorders; Risperidone; Serotonin Antagonists
PubMed: 29695153
DOI: 10.1021/acschemneuro.8b00159 -
Deutsche Medizinische Wochenschrift... Jun 2003
Review
Topics: Animals; Antipsychotic Agents; Basal Ganglia Diseases; Dopamine Antagonists; Dyskinesia, Drug-Induced; Humans; Hypotension, Orthostatic; Risperidone; Schizophrenia; Serotonin Antagonists
PubMed: 12802745
DOI: 10.1055/s-2003-39970 -
The Cochrane Database of Systematic... Jan 2006Risperidone, an atypical antipsychotic, is used to treat mania both alone and in combination with other medicines. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Risperidone, an atypical antipsychotic, is used to treat mania both alone and in combination with other medicines.
OBJECTIVES
To review the efficacy and tolerability of risperidone as treatment for mania.
SEARCH STRATEGY
The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies December 2004), The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched in December 2004. Reference lists and English language textbooks were searched; researchers in the field and Janssen-Cilag were contacted.
SELECTION CRITERIA
Randomised controlled trials comparing risperidone with placebo or other drugs in acute manic or mixed episodes.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data from trial reports. Janssen-Cilag was asked to provide missing information.
QUALITY ASSESSMENT
As in other trials of treatment for mania, the high proportion of imputed efficacy data resulting from rates of failure to complete treatment of between 12% and 62% may have biased the results.
MAIN RESULTS
Six trials (1343 participants) of risperidone as monotherapy or as adjunctive treatment to lithium, or an anticonvulsant, were identified. Permitted doses were consistent with those recommended by the manufacturers of Haldol (haloperidol) and Risperdal (risperidone) for treatment of mania and trials involving haloperidol allowed antiparkinsonian treatment. Risperidone monotherapy was more effective than placebo in reducing manic symptoms, using the Young Mania Rating Scale (YMRS) (weighted mean difference (WMD) -5.75, 95% confidence interval (CI) -7.46 to -4.04, P<0.00001; 2 trials) and in leading to response, remission and sustained remission. Effect sizes for monotherapy and adjunctive treatment comparisons were similar. Low levels of baseline depression precluded reliable assessment of efficacy for treatment of depressive symptoms. Risperidone as monotherapy and as adjunctive treatment was more acceptable than placebo, with lower incidence of failure to complete treatment (RR 0.66, 95% CI 0.52 to 0.82, P = 0.0003; 5 trials). Overall risperidone caused more weight gain, extrapyramidal disorder, sedation and increase in prolactin level than placebo. There was no evidence of a difference in efficacy between risperidone and haloperidol either as monotherapy or as adjunctive treatment. The acceptability of risperidone and haloperidol in incidence of failure to complete treatment was comparable. Overall risperidone caused more weight gain than haloperidol but less extrapyramidal disorder and comparable sedation.
AUTHORS' CONCLUSIONS
Risperidone, as monotherapy and adjunctive treatment, is effective in reducing manic symptoms. The main adverse effects are weight gain, extrapyramidal effects and sedation. Risperidone is comparable in efficacy to haloperidol. Higher quality trials are required to provide more reliable and precise estimates of its costs and benefits.
Topics: Antipsychotic Agents; Bipolar Disorder; Chemotherapy, Adjuvant; Haloperidol; Humans; Lithium; Randomized Controlled Trials as Topic; Risperidone
PubMed: 16437472
DOI: 10.1002/14651858.CD004043.pub2 -
American Journal of Health-system... Sep 2004The pharmacology, pharmaceutics, clinical efficacy, adverse effects, cost, and dosage and administration of long-acting risperidone injection are reviewed. (Review)
Review
PURPOSE
The pharmacology, pharmaceutics, clinical efficacy, adverse effects, cost, and dosage and administration of long-acting risperidone injection are reviewed.
SUMMARY
Risperidone is the first atypical antipsychotic available in a long-acting injectable formulation. After a single injection, significant plasma levels of the drug are achieved at week 3 and sustained through week 6, subsiding by weeks 7-8. Steady state is achieved after four injections. Peak levels are less than those seen with comparable doses of oral risperidone. A 12-week double-blind placebo-controlled study and a one-year open-label study demonstrated the efficacy, safety, and tolerability of long-acting risperidone injection in patients with schizophrenia and schizoaffective disorder. Those who were considered stable on their previous medication showed continued clinical improvement and an increase in health-related quality of life during a year of treatment with long-acting risperidone injection. In the 12-week study, risperidone was well tolerated, with adverse-effect rates similar to those seen with placebo. Weight gain with long-acting risperidone injection is similar to that found with oral treatment. Extrapyramidal symptom ratings have shown improvement from baseline following administration of this agent. Individuals with schizophrenia who previously received oral risperidone therapy have shown a reduction in prolactin levels after a switch to the long-acting formulation.
CONCLUSION
With its unique tolerability and efficacy, long-acting risperidone injection has the potential to extend the benefits of assured medication delivery and improved long-term outcomes to more patients with schizophrenia.
Topics: Antipsychotic Agents; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Double-Blind Method; Humans; Injections; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia
PubMed: 15462250
DOI: 10.1093/ajhp/61.17.1792 -
Drugs in R&D Jun 2015Antipsychotics, risperidone, and risperidone's active metabolite, paliperidone (9-hydroxyrisperidone), are related molecules used for the treatment of schizophrenia and... (Review)
Review
Antipsychotics, risperidone, and risperidone's active metabolite, paliperidone (9-hydroxyrisperidone), are related molecules used for the treatment of schizophrenia and related disorders. Differences in receptor binding, 5-HT2A/D2 (serotonin/dopamine) binding ratios, and mitochondrial proteomics suggest that the effects of risperidone and paliperidone on neuronal firing, regulation of mitochondrial function, and movement are different. This review seeks to explore the most significant differences at the molecular level between risperidone and paliperidone, as reported in preclinical studies. Although risperidone shows higher affinity for 5-HT receptors, paliperidone does not fit this profile. Thus, the risperidone 5-HT2A/D2 binding ratio is significantly lower than the paliperidone 5-HT2A/D2 binding ratio. Paliperidone, similar to lithium and valproate, affects expression levels and phosphorylation of complex I and V proteins in synaptoneurosomal preparations of rat prefrontal cortex, suggesting that paliperidone behaves as a mood stabilizer. It is apparent that the presence of a hydroxyl group in the paliperidone molecule confers increased hydrophilicity to this drug compared with its parent, risperidone; thus, this contributes to differential effects on mitochondrial movement, protein expression, and phosphorylation. These differences are reflected in synaptic plasticity and neuronal firing and have only recently been implicated in the mechanisms of mitochondrial function and movement.
Topics: Animals; Antipsychotic Agents; Dopamine D2 Receptor Antagonists; Humans; Paliperidone Palmitate; Risperidone
PubMed: 25943458
DOI: 10.1007/s40268-015-0092-x